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Infection and Immunity, April 2006, p. 2215-2223, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2215-2223.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Novel Staphylococcus aureus Vaccine: Iron Surface Determinant B Induces Rapid Antibody Responses in Rhesus Macaques and Specific Increased Survival in a Murine S. aureus Sepsis Model

Nelly A. Kuklin,1 Desmond J. Clark,1 Susan Secore,1 James Cook,1 Leslie D. Cope,1 Tessie McNeely,1 Liliane Noble,1 Martha J. Brown,1 Julie K. Zorman,1 Xin Min Wang,1 Gregory Pancari,1 Hongxia Fan,1 Kevin Isett,1 Bruce Burgess,1 Janine Bryan,1 Michelle Brownlow,1 Hugh George,1 Maria Meinz,1 Mary E. Liddell,1 Rosemarie Kelly,1 Loren Schultz,1 Donna Montgomery,1 Janet Onishi,1 Maria Losada,1 Melissa Martin,1 Timothy Ebert,1 Charles Y. Tan,1 Timothy L. Schofield,1 Eszter Nagy,2 Andreas Meineke,2 Joseph G. Joyce,1 Myra B. Kurtz,1 Michael J. Caulfield,1 Kathrin U. Jansen,3 William McClements,1 and Annaliesa S. Anderson1*

Merck and Co. Inc., 440 Sumneytown Pike, WP16 100, West Point, Pennsylvania 19486,1 Intercell AG, Vienna Biocenter 6, A-1030 Vienna, Austria,2 Vaxgen Inc., 1000 Marina Boulevard, Brisbane, California 940053

Received 11 October 2005/ Returned for modification 5 December 2005/ Accepted 17 December 2005

Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.

* Corresponding author. Mailing address: Merck and Co. Inc., 440 Sumneytown Pike, WP16 100, West Point, PA 19486. Phone: (215) 652-3138. Fax: (215) 652-2142. E-mail: liesa_anderson{at}merck.com.

Editor: D. L. Burns

Infection and Immunity, April 2006, p. 2215-2223, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2215-2223.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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